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Sarcoidosis
Overview Sarcoidosis is the collection and clumping of inflammatory cells in the organs of the body. This "inflammatory disease that results in the formation of granulomas" typically affects the lungs and the lymph nodes but can also form at organs such as the eyes, spleen, liver, or brain. Granulomatous lesions form and appear on X-rays, which are normally found because of other medical issues. The risk of getting Sarcoidosis is mostly genetic, but other variants of the disease can occur for other reasons. After the inflammatory response is completed and the site of injury has been healed, the inflammatory cells remain at site. Typically, Sarcoidosis is found in the lungs and can cause coughing, wheezing, shortness of breath and even chest pain. Often times granulomas are found via X-rays of the chest in which lymph nodes are enlarged as well as clear granulomas and scarring of the lungs. Overtime, pulmonary Sarcoidosis can lead to lung fibrosis which can become fatal due to respiratory failure. Genotype and Phenotype Association There are three Genotypes that apply to the genetic disposition of getting Sarcoidosis. Having the genotypes AA or AG code for having either moderately low odds of development or typical odds of development, respectively. However, having the GG genotype (like John Burke) means that someone has Moderately higher odds of development. Although Sarcoidosis is relatively rare, it is reported to be more common in African Americans and people with Scandinavian roots. According to 23andMe.com, people with the GG genotype are 1.6 times more likely to experience sarcoidosis. Typically, Sarcoidosis is prevalent in people who are between the ages of 20 and 40 but can be found in people of all ages. SNP and Gene Association The GG genotype for this disorder is located on the ANXA11 (Annexin 11) gene at marker rs1049550. It is located on chromosome 10q22.3 and is associated with essential biological functions such as calcium signaling, cell growth, and apoptosis. The inability for the inflammation to go away is due to impaired inflammatory cells that can not induce apoptosis. The SNP rs1049550 is considered to be nonsynonymous, meaning that there is a genetic mutation in which the codon codes for a different amino acid. This is known to cause higher susceptibility in people that carry this trait. The first genome association study on Sarcoidosis was conducted using over 440,000 SNP's. Although 23andMe.com does not provide information about other SNP's that can cause this disorder, SNP's rs2789679 and rs7091565 on the ANXA11 gene are associated with Sarcoidosis. According to SNPedia, rs1953600, rs2573346, rs2784773, and rs1049550 (the SNP of interest for John Burke) "are all tightly linked" on the ANXA11 gene. Understanding the Genotype Just because John Burke has the genotype that puts him at a higher risk for this disorder it does not mean that he has or will experience it. Despite this, Sarcoidosis is common with Scandinavian history and and John Burke's ancestry is 3.6% Scandinavian. The fact that he is 99.7% Northern European can explain why he has an elevated risk of this disorder. The best plan of action for John Burke is to not panic. This disorder is very manageable with anti-inflammatory steroids if necessary, but Sarcoidosis may go away by itself. Rarely is this disorder fatal, however, it can cause permanent organ damage in some cases. The chances of Sarcoidosis being fatal or causing long term damage is slim. References 1. 23 and Me 2.SNPedia 3. First Independent Replication study Confirms the strong genetic association of ANXA11 with Sarcoidosis (NCBI) 4. Association of ANXA11 genetic variation with sarcoidosis in African Americans and European Americans (NCBI) 5. Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han Chinese population: a case–control study